The biological activities of many pharmaceuticals, fragrances, food additives and agrochemicals are often associated with their absolute molecular configuration. Enantiomers are identical with respect to certain physical properties, such as melting and boiling points. However, enantiomers may differ in their chemical properties, particularly within biological systems. While one enantiomer may confer a desired biological function through interactions with natural binding sites, another enantiomer may not demonstrate the same function and, in some cases, may present deleterious side effects.
For example the teratogenic effects of the drug thalidomide is likely due to only one enantiomer of the drug, while the other enantiomer is believed to be a safe and useful tranquilizer devoid of teratogenic side effects. Consequently, the preparation of pharmaceutical agents as substantially pure enantiomers can offer therapeutic advantages as compared to the corresponding racemic mixture.
In view of the advantages associated with the administration of substantially pure enantiomers, chemists have explored many approaches for acquiring enantiomerically pure compounds including the resolution of the racemates using chiral stationary phases, structural modifications of naturally occurring chiral substances (as reagents for running stereospecific reactions) and asymmetric catalysis using chiral catalysts or enzymes.
Optically active catalysts or enzymes have limited application in multiple step and kilo scale processes due to their high prices. Similarly the use of chiral stationary phases, for optical resolution, is a very expensive means for kilo scale production.
What is needed, therefore, is a simplified and economical method for the stereospecific synthesis of therapeutic compounds.